The objectives of the proposed work as follows: In collaboration with Professor Wilbur H Sawyer, M.D., Ph. D., Dept. of Pharmacology, College of Physicians & Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032 to design and synthesize the following peptides for potential clinical application: 1) Effective in vivo antagonists of oxytocin, 2) Antagonists of the Antidiuretic Response to arginine vasopressin (AVP), 3) Antagonists of the pressor response to AVP, 4) Natriuretic/diuretic peptides, 5) AVP analogs with enhanced pressor/antidiuretic (P/A) selectivity. An additional objective is: 6) To continue to provide other investigators with samples of synthetic peptides for their independent investigations. Results to date for objective 1,2 and 3 are highly encouraging. We have synthesized a number of analogues of oxytocin which posses potent antagonism to the in vivo oxytocic effects of oxytocin in the rat. These analogues are 1) (Deamino Penicillamine, Tyr (Me), ornithine vasotocin, 2) d Et2 Tyr (Me) OVT, and 3) d(CH2)5 Tyr (Me) OVT. Their in vivo PA2 values are in the range of 7.15 - 7.37. We have also synthesized two analogues of AVP which are the most potent antagonists of the vasopressor effects of AVP. These are A) d(CH2)5AVP, (pA2, 8.35) and B) d(CH2)5 Tyr(Me)AVP, (pA2, 8.62). In addition, modifications of A and B have resulted in partial antagonists of the antidiuretic effects of AVP. These findings have provided very useful clues to the design of even more potent antagonists of oxytocin and AVP. Antagonists 1-3 have potential value for a) the prevention of premature labor, b) probing the possible importance of vasopressin in cardiovascular regulation in normal and pathophysiological states, and c) the treatment of SIADH, respectively.